Page 280 - ebook

[E. Immunology] E-9

Competitively Inhibited Interaction Of Inflammatory

Transcription Factors And Importins By Cell-Permeable

Nuclear Localization Sequence Attenuates The Severity Of

COVID-19

Dongho Kim¹, Gyunam Kim¹, Dasom Shin¹, Seokwon Lee¹, Sanghyeon Yu¹, Misuk Baek¹, Jaewook Lee¹,

Hyemin Yu¹, Joohyun Pi¹, Mingu Kang¹, Jieun Kim¹, Sujeong Kim¹, Eunna Chung¹, Daewoong Jo¹*

¹Immune Disease Team, Cellivery Therapeutics, Inc., Seoul 03929, Korea

The worldwide outbreak of coronavirus disease 19 (COVID-19) is caused by infection with the severe acute

respiratory syndrome (SARS)-CoV-2 virus which induces the excessive secretion of pro-inflammatory cytokines,
known as “cytokine storm”. The uncontrolled production of pro-inflammatory cytokine due to SARS-CoV-2 infection

can be suppressed by regulation of nuclear translocation of inflammation-associated transcription factors (IATFs)
such as NF-κB, STAT1/3, AP-1 & NFAT. To regulate the nuclear translocation of IATFs, an improved cell-permeable

nuclear import inhibitor (iCP-NI) has been developed by fusing sequence-optimized advanced macromolecule
transduction domains (aMTDs) and nuclear localization sequence (NLS) originated from human NF-κB. In brief, iCP-

NI decreased lethality of RNA virus infection mimetic pneumonitis animals by reduction of the inflammatory
cytokines in lungs. iCP-NI also significantly attenuates the severity of the SARS-CoV-2 infected syrian hamster model.

The reduction of viral replication is proved with quantitative PCR by decreasing the level of RdRp gene (log7.04 vs
log5.79). Furthermore, the inflammatory cytokine genes are significantly decreased and the lung structures from

inflammation-mediated damages are protected. As a result, the iCP-NI could be developed as a novel anti-
inflammatory immune-therapeutic agent for severe inflammatory diseases including COVID-19.